Two key NIMH objectives pertain to (a) the discovery of 'markers' that can be used to identify individuals at risk of psychiatric disease and (b) the development of preventative treatment measures to pre-empt the onset of disorder in these individuals. The proposed research seeks to further these objectives in the context of anxiety disorders. It investigates the neurocognitive mechanisms through which trait vulnerability to anxiety is conferred and examines whether cognitive and neurocognitive training can be used to restore function in areas of impairment. In addition, it explores whether neural markers can be used to identify those individuals 'at- risk' of anxiety disorders who are most likely to benefit from preventative cognitive training interventions. Functional magnetic resonance imaging (fMRI) will be used to test a dual route model of trait vulnerability to anxiety, the contention being that at least two, largely independent, sources of individual variability confer vulnerability to anxiety disorders. Our first specific aim is to establish whether (i) impoverished recruitment of frontal control mechanisms and (ii) enhanced amygdala responsivity to cues that signal threat are independently associated with trait vulnerability to anxiety. Both attention and fear conditioning fMRI experiments will be conducted in healthy volunteers with varying levels of trait anxiety. We aim to establish whether trait anxiety-related dysregulation of frontal function encompasses both dorsolateral and ventromedial prefrontal regions, with disruption to the former impacting the regulation of attention, and disruption to the latter impacting the down-regulation and extinction of conditioned fear. Our second specific aim is to establish whether trait anxious individuals primarily characterised by frontal hypo-activity will benefit from attention and emotion regulation training to a greater extent than those primarily characterised by amygdala hyper-responsivity. Here, we will also investigate whether the benefits of attention and emotion regulation training can be augmented by provision of neurofeedback from the frontal regions supporting these processes. We will examine whether these training procedures can be used to restore impoverished dorsolateral and ventromedial prefrontal function, and we will investigate the impact of this upon sustained attention and the down-regulation and extinction of conditioned fear. PUBLIC HEALTH RELEVANCE: For nearly 20% of the population, having an Anxiety Disorder causes serious disruption to everyday life. The proposed research uses brain imaging techniques to divide individuals at high risk of Anxiety Disorders into those who show low activity in frontal regions of the brain used to control attention and emotional responses versus those who show heightened activity in the amygdala, a region involved in detecting signs of danger. This will enable us to test the prediction that the former group will benefit to a greater extent from training procedures aimed at improving attention and the regulation of negative emotions.